Do CYP2C19 and ABCB1 gene polymorphisms and low CYP3A4 isoenzyme activity have an impact on stent implantation complications in acute coronary syndrome patients?

Abstract

Aim

The aim of this study was to determine the impact of CYP2C19 and ABCB1 gene polymorphisms and CYP3A4 isoenzyme activity on stent implantation complications among patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).

Patients and methods

Seventy-six patients (median age 63, range 37–91 years) with an ACS who underwent PCI were screened for CYP2C19 and ABCB1 gene polymorphisms with real-time polymerase chain reaction: CYP2C19*2, CYP2C19*17, and ABCB1 3435. CYP3A4 isoenzyme activity was determined by urine cortisol and 6-beta-hydroxycortisol levels. Stent implantation complications such as stent thrombosis (n=2) and restenosis (n=1) were observed among drug-eluting stent recipients.

Results

Low mean 6-beta-hydroxycortisol/cortisol ratio is indicative of impaired CYP3A4 activity and was associated with higher risk of thrombosis (b coefficient=0.022, SE 0.009, p=0.021 in the linear regression model). The increase in the length of the implanted stent was associated with higher risk of restenosis (b coefficient=0.006, SE=0.002, p=0.001 in the linear regression model). The presence of the CYP2C19*2 polymorphism did not affect the incidence of stent thrombosis (b coefficient=−1.626, SE=1.449, p=0.262 in the logistic regression model), nor did the CYP2C19*17 (b coefficient=−0.907, SE=1.438, p=0.528 in the logistic regression model) and ABCB1 3435 polymorphisms (b coefficient=1.270, SE=1.442, p=0.378 in the logistic regression model).

Conclusion

We did not find evidence that the presence of CYP2C19*2, CYP2C19*17, and ABCB1 3435 polymorphisms may jeopardize the safety of stent implantation in patients with an ACS. Patients with low CYP3A4 isoenzyme activity may have increased risk of stent thrombosis.

Keywords:

• acute coronary syndrome
• clopidogrel
• complications
• polymorphism
• stents

Author contributions

E Rytkin and KB Mirzaev conceived the study, acquired and analyzed the data, and drafted the manuscript. EA Grishina, VV Smirnov, KA Ryzhikova, and ZhA Sozaeva conceived the study, acquired and analyzed the data, and critically revised the manuscript. MI Giliarov, DA Andreev, and DA Sychev conceived the study and critically revised the manuscript. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.